Modern cancer therapy relies strongly on the use of ionizing irradiation, either alone or in combination with surgery or chemotherapy, as a primary strategy for the treatment of malignancies of various types. Ionizing radiation induces multiple and varying biochemical events in various cell types which determine the ability of the cell to survive the radiation challenge.
Treatment of tumors and hyperproliferative diseases with ionizing radiation (hereinafter referred to also as “cancer radiotherapy”) is used extensively in cancer therapy. The goal of such treatment is to elicit the destruction of tumor cells and to inhibit tumor cell growth presumably through DNA damage, while attempting to cause minimum damage to non-tumor cells and tissues. Collateral damage to adjacent tissues often limits the radiation doses applied, thus limiting the effectiveness of radiotherapy of certain tumors, such as brain tumors and tumors in the abdominal cavity and the neck.
Mesna (sodium 2-sulfanylethanesulfonate) is a highly water soluble organosulfur compound known to be used as an adjuvant in cancer chemotherapy involving cyclophosphamide and ifosfamide for the prophylaxis of urothelial toxicity.
A few scientific publications describe the use of Mesna in association with colitis or proctitis. Shusterman et al. (Digestive Diseases and Sciences 2003; 48(6):1177-85) discloses treatment of rats with Mesna after exposure to trinitrobenzene sulfonic acid (TNB) as a model of inflammatory bowel disease.
Kumar et al (Gynecol Oncol. 1994; 54(3):307-315) reports a clinical study of patients with squamous cell carcinoma of the cervix who were received various therapies, including, ifosfamide-mesna, following radiotherapy.
The pharmacokinetics (PK) and clinical efficacy of intravenous versus intravenous/oral Mesna in patients receiving ifosfamide for soft tissue sarcoma have been studied by Mace (Clin. Cancer. Res., 2003; 9:5829-5834) where i.v./oral Mesna regimen was found to be at least as uroprotective as the approved i.v. regimen.
WO 2005/117851 discloses methods of prevention, amelioration and treatment of enteritis induced by radiation therapy for the treatment of gastrointestinal malignancies, by administering the anti-inflammatory drug balsalazide to a patient in need thereof.
WO 2007/038428 discloses methods for preventing, treating or ameliorating gastrointestinal (GI) and bladder disorders induced by or associated with chemotherapy or radiation therapy in an animal by administering to the animal active vitamin D compounds. WO 2007/038428 further discloses chemotherapeutic agents including Mesna for the treatment of cancer.
U.S. Patent Application Publication No. 2004/0023925 discloses methods for enhancing the efficacy of conventional cancer therapies such as surgery, chemotherapy and radiation by combining said therapies with the use of a therapeutic material which binds to and interacts with galectins. This publication further discloses pharmaceutical agents that may be used for the combination chemotherapy, among which Mesna is listed as a chemotherapeutic agent.
There remains an unmet need for improved and efficient methods, devoid of adverse systemic effects, for preventing or reducing gastrointestinal tract injury induced by radiation therapy.